CD44 variant isoforms are involved in plasma cell adhesion to bone marrow stromal cells

被引:45
作者
Van Driel, M
Günthert, U
van Kessel, AC
Joling, P
Stauder, R
Lokhorst, HM
Bloem, AC
机构
[1] Univ Utrecht Hosp, Dept Immunol, NL-3584 CX Utrecht, Netherlands
[2] Basel Inst Immunol, CH-4058 Basel, Switzerland
[3] Univ Utrecht Hosp, Dept Hematol, NL-3584 CX Utrecht, Netherlands
[4] Univ Utrecht Hosp, Dept Pathol, NL-3584 CX Utrecht, Netherlands
[5] Univ Innsbruck Hosp, Dept Internal Med, A-6020 Innsbruck, Austria
关键词
multiple myeloma; adhesion; stromal cells; CD44 variant molecules; CD44v;
D O I
10.1038/sj.leu.2402336
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells correlates with unfavorable prognosis, suggesting that CD44 variant molecules are involved in the disease process. In this study, the presence of CD44v on B cell lines from different stages of development was analyzed by flow cytometry and a role in adhesion to stromal cells from different tissues was evaluated in in vitro binding assays. CD44v3, v6 and v9 isoforms were exclusively expressed on plasma cell lines and CD44v9 expression correlated with IL-6-dependent plasma cell growth. Binding studies using CD44 isoform-specific reagents showed that CD44v6 and CD44v9 were involved in binding to bone marrow stromal cells, but not to in vitro synthesized ECM or hyaluronic acid. CD44v9-mediated plasma cell binding resulted in a significant induction of IL-6 secretion by bone marrow stromal cells. Large differences in quantitative plasma cell binding to stromal cells from different tissues were observed. These, however, could not be related to a differential use of CD44v in these binding processes. The role of CD44v9 in adhesion induced IL-6 secretion and its preferential expression on IL-6-dependent plasma cell lines may explain the previously observed correlation between CD44v9 expression and adverse prognosis in multiple myeloma.
引用
收藏
页码:135 / 143
页数:9
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